Abstract: :
Purpose: There are no lymphatic channels within the eye. Therefore,retinoblastoma, like uveal melanoma, spreads exclusively bya hematogenous route unless the conjunctiva is involved by extraocularextension. In uveal melanoma, the looping matrix patterns arenot blood vessels, but they connect to blood vessels. Theseextravascular matrix patterns have been shown to conduct fluidin vitro and in vivo. Moreover, the presence of these patternshistologically is associated with death from metastatic uvealmelanoma, consistent with observations from in vitro studiesassociating pattern formation by the tumor cell to highly invasivemelanoma cells. Looping extravascular matrix patterns are notrestricted to uveal melanoma and are found in cutaneous melanoma,ovarian carcinoma, and inflammatory breast cancer. This studywas designed to investigate the possibility that looping extravascularmatrix patterns might be present in invasive retinoblastoma.Methods: All retinoblastomas accessioned by the OphthalmicPathology Laboratory at the Hadassah University Hospital between1990 and 2001 (76) were available for histological study. Ofthese, 28 cases originated from a Hadassah outreach clinicsin Kenya or Malawi. Serial sections were stained with hematoxylin-eosinand with periodic acid-Schiff (PAS) without counterstaining,a method used to detect extravascular matrix patterns in uvealmelanoma with high reproducibility.Results: Each eye containedretinoblastoma within the retina and/or vitreous: invasion intothe retrolaminar compartment of the optic nerve was detectedin 18/73 cases (25%; in 3 cases, we could not assess optic nerveinvasion), choroidal invasion in 31/76 cases (49%), and extraocularextension in 17/76 cases (22%). PAS-positive patterns were detectedin the intraocular component of 5/76 eyes (7%) and were notseen in any of the zones of retrolaminar optic nerve invasion.In eyes that featured choroidal invasion or extraocular extension,extravascular matrix patterns were present in 22/31 (71%) and12/17 (71%) of the invasive tumor components respectively.Conclusions: The expression of extravascular matrix patternsin retinoblastoma appears to reflect the presence of an invasiveretinoblastoma phenotype. However, the formation of these patternsgenerally requires a permissive microenvironment because thesepatterns are not seen in optic nerve invasion but are identifiedin the collagen-rich environment of the choroid and within orbitalsoft tissue.